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Table of Contents
About the reports
Summary of key findings
Background information about omega-3 and omega-6 fatty acids &
their known functions
Products available
Omega-3 fatty acids for cardiovascular health and disease [1-3]
Omega-3 fatty acids for asthma [4]
Omega-3 fatty acids for other diseases [5]
Omega-3 fatty acids and cognitive function, dementia, and
neurological diseases [6]
Omega-3 fatty acids for organ transplantation [7]
Safety aspects of omega-3 fatty acids [3]
References
About the reports
This document summarizes the results of eight evidence-based
reviews on the effects of omega-3 fatty acids from food or
dietary-supplement sources for the prevention and treatment of
several diseases. These reviews were prepared under contract to
the Agency for Healthcare Research and Quality (AHRQ). All
reviews were sponsored and funded by the Office of Dietary
Supplements (ODS) of the National Institutes of Health, U.S.
Department of Health and Human Services. Five reports were
published in March 2004 and 3 additional reports were published
in February 2005, all of which are available in their entirety
and summary form on the ODS web site (ods.od.nih.gov)
and the AHRQ web site (www.ahrq.gov).
Three reports focus on cardiovascular disease (CVD), including
the effects of omega-3 fatty acids on cardiac electrophysiology
and arrhythmia (the heart's beating rate and disorders of its
rhythm), cardiovascular risk factors such as blood pressure, and
intermediate markers of disease such as heart rate variability
[1-3]. One report focuses on omega-3 fatty acids and asthma.
Another report addresses the effects of omega-3 fatty acids on
type II diabetes and the metabolic syndrome, inflammatory bowel
disease, rheumatoid arthritis, renal disease, systemic lupus
erythematosus, and osteoporosis [5]. Another report addresses
the effects of omega-3 fatty acids on cognitive function in
normal aging, the incidence and treatment of dementia, the
incidence of Parkinson's disease and cerebral palsy in infants,
and clinical outcomes in progressive multiple sclerosis [6].
Another report evaluates whether omega-3 fatty acids improve the
outcomes of patients undergoing organ transplantation [7]. These
reports were prepared by the Tufts-New England Medical Center
Evidence-based Practice Center (Tufts EPC) [1,2,3,4], the
University of Ottawa Evidence-based Practice Center at the
University of Ottawa, Canada (Ottawa EPC) [5], and the Southern
California/RAND Evidence-based Practice Center in Los Angeles
(RAND EPC) [6,7].
Summary of key findings
·
The polyunsaturated fatty acids alpha-linolenic acid
(ALA) and linoleic acid (LA) must come from the diet because
they cannot be made by the body. ALA, an omega-3 fatty acid, is
converted in the body to the fatty acids eicosapentaenoic acid
(EPA) and docosahexaenoic acid (DHA). LA, an omega-6 fatty acid,
is converted to the fatty acid arachidonic acid (AA).
·
Most American diets provide more than 10 times as much
omega-6 than omega-3 fatty acids. There is general agreement
that individuals should consume more omega-3 and less omega-6
fatty acids to promote good health. Good sources of ALA are
leafy green vegetables, nuts, and vegetable oils such as canola,
soy, and especially flaxseed. Good sources of EPA and DHA are
fish and organ meats. LA is found in many foods, including meat,
vegetable oils (e.g., safflower, sunflower, corn, soy), and
processed foods made with these oils.
·
EPA and DHA are metabolized through the same biochemical
pathways as AA. EPA and AA are precursors for hormone-like
agents known as eicosanoids. It is not known whether a desirable
ratio of omega-6 to omega-3 fatty acids exists or to what extent
high intakes of omega-6 fatty acids interfere with any benefits
of omega-3 fatty acid consumption.
·
Impact on cardiovascular disease: According to both
primary and secondary prevention studies, consumption of omega-3
fatty acids, fish, and fish oil reduces all-cause mortality and
various CVD outcomes such as sudden death, cardiac death, and
myocardial infarction. The evidence is strongest for fish and
fish oil supplements.
·
Impact on heart function: Animal and isolated organ/cell
culture studies demonstrate that omega-3 fatty acids affect
cellular functions involved in ensuring a normal heart rate and
coronary blood flow.
·
Impact on CVD risk factors: Fish oils can lower blood
triglyceride levels in a dose-dependent manner. Fish oils have a
very small beneficial effect on blood pressure and possible
beneficial effects on coronary artery restenosis after
angioplasty and exercise capacity in patients with coronary
atherosclerosis.
·
Impact on asthma: No conclusions could be drawn about the
value of omega-3 fatty acid supplements in the prevention or
treatment of asthma for adults or children other than the fact
that they have an acceptable safety profile.
·
Impact on other conditions: Omega-3 fatty acids can
reduce joint tenderness and need for corticosteroid drugs in
rheumatoid arthritis. Data are insufficient to support
conclusions about the effects of omega-3 fatty acids on
inflammatory bowel disease, renal disease, systemic lupus
erythematosus, bone density, and diabetes.
·
Impact on cognitive function: The quantity and strength
of evidence is inadequate to conclude that omega-3 fatty acids
protect cognitive function with aging or the incidence or
clinical progression of dementia (including Alzheimer's
disease), multiple sclerosis, and other neurological diseases.
·
Impact on organ transplantation: No conclusive evidence
suggests specific benefits of omega-3 fatty acid supplementation
on any outcome in any form of organ transplantation. However,
available studies are small, have methodological problems, and
may not fully apply to current transplantation procedures.
·
Safety: Adverse events related to consumption of fish-oil
or ALA supplements are generally minor and typically
gastrointestinal in nature (such as diarrhea). They can usually
be eliminated by reducing the dose or discontinuing the
supplement.
·
Conclusion: The health effects of omega-3 fatty acids
require further investigation. Each report provides
recommendations on specific research needs and how to improve
the quality of future studies.
Background information about omega-3 and omega-6 fatty acids &
their known functions
There are two major classes of polyunsaturated fatty acids
(PUFAs) -- the omega-3 and the omega-6 fatty acids --
distinguished by their chemical structure. Only the fatty acids
alpha-linolenic acid (ALA) and linoleic acid (LA) must come from
the diet because they cannot be made by the body. ALA, an
omega-3 fatty acid, is converted in the body to eicosapentaenoic
acid (EPA) and docosahexaenoic acid (DHA). EPA and DHA also
occur naturally in some foods. LA, an omega-6 fatty acid, is
converted in the body to arachidonic acid (AA). Both EPA and DHA
are metabolized through the same biochemical pathways as AA.
Studies show that omega-3 fatty acids in general decrease
triglyceride and very-low-density lipoprotein blood levels in
hyperlipidemic individuals but may increase or have no effect on
low-density lipoprotein (LDL) levels.
Both AA and EPA are further metabolized to produce hormone-like
agents called eicosanoids, which include prostaglandins,
thromboxanes, and leukotrienes. Eicosanoids regulate fundamental
physiological processes such as cell division and growth, blood
clotting, muscle activity, secretion of digestive juices and
hormones, and movement of substances like calcium into and out
of cells. However, AA and EPA lead to the production of
different subgroups of eicosanoids with sometimes opposing
effects. Eicosanoids formed from AA (particularly the series-2
prostaglandins and series-4 leukotrienes) are released in the
body in response to injury, infection, stress, or certain
diseases. They increase platelet aggregation and enhance
vasoconstriction and the synthesis of substances involved with
the inflammatory process. Eicosanoids derived from EPA
(particularly the series-3 prostaglandins), in contrast,
decrease excessive series-2 prostaglandin production. As a
result, adequate production of EPA-derived series-3
prostaglandins may help protect individuals against heart
attacks and strokes as well as certain inflammatory diseases
such as arthritis, systemic lupus erythematosus, and asthma.
The omega-3 fatty acid DHA, while not involved in eicosanoid
formation, is the major polyunsaturated fatty acid found in the
brain and is important for brain development and function.
Synapses are rich in DHA, which suggests that this fatty acid is
involved in signal transmission along neurons. DHA is also
required to produce one member of a family of compounds called
resolvins that participate in the body's response to
inflammation in the brain. The DHA-derived resolvin in
particular helps to reduce inflammation brought about by
ischemic insults (reductions in blood flow). (EPA also helps to
temper inflammatory responses by decreasing production of
proinflammatory compounds such as cytokines.)
Most American diets provide at least 10 times more omega-6 than
omega-3 fatty acids. There is now general scientific agreement
that individuals should consume more omega-3 and fewer omega-6
fatty acids for good health. It is not known, however, whether a
desirable ratio of omega-6 to omega-3 fatty acids exists for the
diet or to what extent high intakes of omega-6 fatty acids
interfere with any benefits of omega-3 fatty acid consumption.
Tufts EPC investigators reviewed the Third National Health and
Nutrition Examination Survey (NHANES III; 1988-1994) database to
examine intakes of omega-3 fatty acids in the United States.
They found that men consumed significantly less ALA than women,
adults consumed more than children, and those with a history of
CVD consumed less than those without CVD (when energy intake was
taken into account in the analysis). On any given day, only 25%
of the population reported consuming any EPA or DHA. Average
daily intakes were 14 g LA, 1.33 g ALA, 0.04 g EPA, and 0.07 g
DHA.
ALA is present in leafy green vegetables, nuts, vegetable oils
such as canola and soy, and especially in flaxseed and flaxseed
oil. Good sources of EPA and DHA are fish (both finfish and
shellfish and their oils and eggs) and organ meats. LA is found
in many foods consumed by Americans, including meat, vegetable
oils (e.g., safflower, sunflower, corn, soy), and processed
foods made with these oils. The Institute of Medicine has
established Adequate Intakes for ALA and LA (1.1-1.6 g/day and
11-17 g/day, respectively, for adults) but not for EPA and DHA.
Products available
Omega-3 fatty acids are found in a variety of dietary
supplements. For example, products containing flaxseed oil
provide ALA, fish-oil supplements provide EPA and DHA, and algal
oils provide a vegetarian source of DHA.
Omega-3 fatty acids for cardiovascular health and disease [1-3]
Epidemiological studies first published in the late 1970s noted
relatively low cardiovascular mortality in populations such as
Eskimos with high fish consumption. The apparent health benefits
of fish are explained, at least in part, by the EPA and DHA they
contain. Since these early studies, hundreds of observational
and clinical trials have been conducted to evaluate the effects
of EPA and DHA from marine sources and ALA from plant sources on
CVD and its many risk factors and intermediate markers and to
understand the potential benefits of increased intakes of
omega-3 fatty acids.
The three reports by the Tufts EPC focused on different areas of
research concerning this relationship between omega-3 fatty
acids and cardiovascular health and disease and involved
systematic reviews of the available scientific-medical
literature. The first report focused on whole animal and
isolated organ and cell culture studies to assess the effects of
omega-3 fatty acids on arrhythmogenic mechanisms and outcomes.
The second assessed the effects of EPA, DHA, and ALA on various
CVD risk factors and intermediate markers of CVD in healthy
people and people with dyslipidemia, diabetes, or known CVD. The
third reviewed experimental and observational studies that
investigated the effect of dietary or supplemental omega-3 fatty
acids on specific clinical CVD outcomes (e.g., myocardial
infarction and stroke) and whether these substances can play a
role in the primary or secondary prevention of these outcomes.
Animal and isolated organ/cell culture studies [1]
A systematic review and screening of the literature identified
86 studies that met inclusion criteria and provided appropriate
data. Of the 26 studies on living animals, a meta-analysis of 13
studies (with rats and monkeys) that compared the antiarrhythmic
effects of ALA or fish oil with omega-6 fatty acids showed that
fish-oil supplements (but not ALA) significantly reduced risk of
death, ventricular tachycardia, and ventricular fibrillation.
Since the majority of these studies were conducted by one
research group, studies need to be repeated in other
laboratories to confirm these results.
Another 60 studies evaluated the effects of omega-3 fatty acids
on isolated organs and cell cultures. Seven of them reported
that EPA and DHA (and in one instance ALA) protected against
spontaneous or induced arrhythmias in both rat and guinea pig
models. In the presence of various arrhythmogenic agents and
across the species studied, omega-3 fatty acids consistently
decreased the contraction rate and thereby had a protective
effect compared with other substances, including placebos, but
studies that did not administer an arrhythmogenic agent showed
inconsistent results.
Conclusions cannot be drawn about the biochemical or
physiological mechanisms that explain the potential
antiarrhythmogenic effects of omega-3 fatty acids. These fatty
acids affect cell functions (such as the movement of ions into
and out of the cell) that are involved in cardiac
electrophysiology to ensure a normal heart rate and coronary
blood flow.
Cardiovascular risk factors and intermediate markers of CVD
[2]
Many proposed risk factors for, and intermediate markers of, CVD
exist. One report addressed the following risk factors and their
relationship to omega-3 fatty acids in adults: total, LDL, and
high density lipoprotein (HDL) cholesterol; triglycerides;
lipoprotein (a); apolipoprotein (apo) A1; apo B; apo B-100 and
LDL apo B; systolic and diastolic blood pressure; fasting
insulin; C-reactive protein; fibrinogen; blood clotting factors
VII, VIII, and von Willebrand factor; and platelet aggregation.
The intermediate markers of CVD reviewed were coronary artery
restenosis after angioplasty, carotid artery intima-media
thickness, exercise tolerance testing, and heart rate
variability. The literature review excluded studies of children,
studies of daily omega-3 fatty acid intakes greater than 6
g/day, and studies less than 4 weeks long. A total of 123
articles that meet final eligibility criteria were reviewed
regarding 23 potential risk factors and intermediate markers of
CVD and tissue levels of omega-3 fatty acids. For most outcomes
of interest, analysis was confined to the largest randomized
trials.
Overall, strong evidence showed that fish-oil supplements had a
substantial and beneficial effect on triglycerides that was
greater with larger intakes of fish oil; most studies reported a
net decrease of about 10-33%. There is also evidence of a very
small beneficial effect of fish oils on blood pressure and
possible beneficial effects on coronary artery restenosis after
angioplasty, exercise capacity in patients with coronary
atherosclerosis, and heart rate variability (particularly in
patients with recent myocardial infarctions). No consistent
beneficial effects were apparent for the other CVD risk factors
or intermediate markers analyzed. Regarding concerns that
glucose tolerance might be adversely affected by omega-3 fatty
acids, there was no consistent evidence of a detrimental effect.
Meta-regression analysis of 50 trials showed that the dose of
omega-3 fatty acids consumed was related to changes in EPA and
DHA levels -- as plasma or serum phospholipids, platelet
phospholipids, or in erythrocyte membranes -- without the
influence of other factors. Supplementing the diet with 1-g of
EPA and/or DHA resulted in approximately a 1% increase in the
level of EPA and DHA and also to increases in granulocyte and
monocyte membrane phospholipid levels. Few data are available,
however, on how the effect of omega-3 fatty acids on CVD risk
factors and intermediate markers differs depending on people's
underlying health status and risk of CVD, amount of omega-3
fatty acids consumed, duration of consumption, or source or type
of these fatty acids. In particular, the potential effects of
ALA are unknown.
Cardiovascular disease [3]
One report examined how dietary or supplemental omega-3 fatty
acids affect specific CVD outcomes such as myocardial infarction
and stroke and investigated whether these fatty acids can play a
role in the primary and secondary prevention of these outcomes.
A systematic review of the literature and subsequent screening
identified 39 studies that met the investigators' inclusion
criteria for reporting mortality or CVD clinical outcomes with a
follow-up of at least one year. The primary prevention studies
included 22 prospective cohort studies and only one randomized,
controlled trial (RCT); they were conducted in countries around
the world, most cohorts had several thousand subjects, and
studies lasted from 4 to 30 years. The secondary prevention
studies, in contrast, consisted of 11 RCTs and one prospective
cohort study that reported outcomes on CVD populations; they
included over 16,000 patients and lasted from 1.5 to 5 years.
Overall, evidence from both the primary and secondary prevention
studies supports the hypothesis that consumption of omega-3
fatty acids, fish, and fish oil reduces all-cause mortality and
various CVD outcomes such as sudden death, cardiac death, and
myocardial infarction. The evidence is strongest for fish or
fish oil whereas the potential effects of ALA are largely
unknown and the relative effects of ALA versus fish oil are not
well defined. In the only RCT that directly compared ALA and
fish oil, both treatments reduced CVD outcome. No consistent
differences in the effects of omega-3 fatty acids on CVD
outcomes were found between men and women, largely because the
proportion of women in RCTs was small and data from men and
women were not analyzed separately to address any differences.
Data were also insufficient to determine the optimal quantity
and type of omega-3 fatty acids to consume or to identify an
optimal ratio of omega-3 to omega-6 fatty acid intake, if one in
fact exists.
The lessons to be drawn from all these studies to date regarding
use of omega-3 fatty acids for preventing and treating CVD are
not completely clear. Because the studies involved a variety of
methods of estimating fish or omega-3 fatty acid intake,
background diets, background risk for heart disease, settings,
and methods for reporting results, the validity of applying the
results of studies conducted outside the United States to the
U.S. population is uncertain. Furthermore, dietary intervention
trials are limited by the multiple and complex dietary changes
in the trials that make it difficult to distinguish among
components and determine which specific components or
combinations of these diets are most beneficial. For example,
the different types of fish consumed and the method of food
preparation may cause different effects.
Omega-3 fatty acids for asthma [4]
Asthma is a major public health concern for Americans. In 1987
it was hypothesized that the low incidence of asthma among
Eskimos resulted from their high intakes of oily fish rich in
EPA and DHA. Basic research suggests that omega-3 fatty acids
may affect asthma because they influence substances that are
part of the inflammatory process involved with asthma, such as
the series-2 prostaglandin PGE2.
The Ottawa EPC conducted a comprehensive search of the published
and unpublished scientific-medical literature. Its screening
process identified 31 reports describing 26 studies. The primary
outcome measure evaluated was the forced expiratory volume in
one second, considered the best available method to assess
pulmonary function. It was not possible to conduct a
meta-analysis with the RCTs because of problems and limitations
such as flawed designs, missing data, and incompatible study
variables; most were small and lacked the ability to detect a
statistical difference between the treatments, and inclusion and
exclusion criteria were rarely reported.
Conclusions could not be made about the value of omega-3 fatty
acid supplements in asthma for adults or children beyond that
they have an acceptable safety profile. The evaluation of ten
RCTs and nine other studies found the results to be too
inconsistent and of limited applicability to larger groups of
people to conclude that these supplements are an efficacious
adjuvant or monotherapy. In some cases, asthma medications used
by the subjects may have prevented the identification of any
benefits from the omega-3 supplements. No other characteristics
of the treatment (such as the type of fatty acid used, specific
source, daily dose, and intervention length) were found to
improve respiratory outcomes. As to whether omega-3 fatty acids
influence substances that are part of the inflammatory process,
such as PGE2, the 11 relevant studies were
insufficient to address this issue because of small sample sizes
and differing methodologies.
Whether omega-3 fatty acids are effective in the primary
prevention of asthma is unknown. Four observational studies in
children support a positive association for dietary patterns
that include all fish or oily fish, but a prospective study of
adult nurses found no association between asthma onset and
dietary fish intake. One RCT is evaluating the relationship in
neonates at risk for asthma whose intake of omega-3 fatty acids
or placebo was initiated before birth. Its interim results show
little benefit from the supplement, though 18 months is probably
too early in life to reliably identify asthma.
Omega-3 fatty acids for other diseases [5]
The RAND EPC conducted a comprehensive search of published and
unpublished scientific-medical literature on the health effects
of omega-3 fatty acids in type II diabetes and metabolic
syndrome, inflammatory bowel disease, rheumatoid arthritis,
renal disease, systemic lupus erythematosus, and bone
density/osteoporosis. Only articles that reported the results of
RCTs or controlled clinical trials were included except for
observational studies of bone mineral status. In all, 83
articles met the inclusion criteria, 82 of which were RCTs.
Overall, the data were insufficient to draw conclusions about
the value of omega-3 fatty acids for these medical problems with
the exception of rheumatoid arthritis.
Type II diabetes and metabolic syndrome
Eighteen of the 34 RCTs whose subjects had type II diabetes or
metabolic syndrome provided sufficient statistics to be included
in a meta-analysis. The analysis found that omega-3 fatty acids
had a favorable effect on triglyceride levels when compared with
placebo but had no effect on total, LDL, or HDL cholesterol;
fasting blood sugar; or glycosylated hemoglobin. A qualitative
analysis of 4 studies concluded that omega-3 fatty acids had no
effect on plasma insulin or insulin resistance in subjects with
either disorder.
Inflammatory bowel disease (Crohn's disease and ulcerative
colitis)
In the 13 studies that reported outcomes in patients with
inflammatory bowel disease, omega-3 fatty acids had variable
effects on assessment scores (clinical, sigmoidoscopic, and
histologic), induced remission, and relapse rates. For
ulcerative colitis, omega-3 fatty acids had no effect on the
relative risk of relapse in a meta-analysis of three studies.
The requirement for corticosteroids among patients receiving
omega-3 fatty acids relative to placebo was not significantly
reduced in two studies. No studies evaluated the effect of
omega-3 fatty acids on the requirements for other
immunosuppressive medications.
Rheumatoid arthritis
A meta-analysis of nine studies of patients with rheumatoid
arthritis concluded that omega-3 fatty acids had no effect on
patients' reports of pain and disease severity, swollen joint
count, or erythrocyte sedimentation rate (a measure of disease
activity). However, an earlier meta-analysis found that the
omega-3 fatty acids produced a statistically significant
improvement in tender joint count as compared with placebo. A
qualitative analysis of seven studies that assessed the effect
of omega-3 fatty acids on anti-inflammatory drug or
corticosteroid requirements found that six demonstrated reduced
requirements. No studies assessed how the supplements affected
requirements for disease-modifying antirheumatic drugs and no
studies used a composite score that incorporated both subjective
and objective measures of disease activity. Overall, omega-3
fatty acids appear to reduce tender joint counts in individuals
with rheumatoid arthritis and may reduce requirements for
corticosteroids. The studies do not demonstrate an effect of the
supplements on other clinical outcomes.
Renal disease
A qualitative analysis of nine studies assessing the effects of
omega-3 fatty acids in renal disease concluded that the
supplements had various effects on serum creatinine and
creatinine clearance but no effect on the progression to
end-stage renal disease. The one study that assessed
hemodialysis graft patency found graft patency to be
significantly better with fish oil than placebo. No studies
assessed whether omega-3 fatty acids altered requirements for
corticosteroids.
Systemic lupus erythematosus
A qualitative analysis of the three studies that assessed the
effects of omega-3 fatty acids in systemic lupus erythematosus
found variable effects on disease activity. No study assessed
their effect on damage or patient perceptions of the severity of
their disease. Omega-3 fatty acids had no effect on
corticosteroid requirements in one study, but no study assessed
how these supplements affected requirements for other
immunosuppressive drugs. No study used both subjective and
objective measures to study disease activity.
Bone density/osteoporosis
A qualitative analysis of five studies described in four reports
found variable effects of omega-3 fatty acids on bone density.
No studies were identified that assessed their effects on
fractures.
Omega-3 fatty acids and cognitive function, dementia, and
neurological diseases [6]
Omega-3 fatty acids appear to be important in brain development
and function. Their effects on cognitive function in normal
aging, incidence and treatment of dementia, incidence of several
neurological diseases, and progression of multiple sclerosis
were evaluated. A comprehensive search of the published and
unpublished scientific-medical literature identified 12 studies
that met inclusion criteria.
Cognitive function in normal aging and dementia
In the one cohort study that assessed the effects of omega-3
fatty acids on cognitive function with normal aging, fish
consumption was only weakly associated with a reduced risk of
cognitive impairment and had no association with cognitive
decline over time; omega-3 fatty acid consumption was not
associated with either outcome. Three prospective cohort studies
evaluated the effects of these compounds on the incidence of
dementia. Fish consumption was associated with a significant
reduction in the incidence of non-Alzheimer's dementia in only
one study. In all three, however, fish consumption was linked to
a reduced risk of Alzheimer's dementia but was statistically
significant in only one study. Total omega-3 fatty acid
consumption and consumption of DHA (but not ALA or EPA) were
associated with a significant reduction in the incidence of
Alzheimer's disease. In the one RCT that assessed the effects of
omega-3 fatty acids for the treatment of dementia, DHA produced
a small improvement in scores on a dementia rating scale, but
the sample size was small and the study was of poor quality.
Multiple sclerosis and other neurological diseases
Two studies (one cohort and one case control) that assessed the
association between omega-3 fatty acid intake and incidence of
multiple sclerosis found no significant results. In three
studies that evaluated omega-3 fatty acid intake on disease
progression, the RCT found no effects on disability or relapse
rates, though the two single-arm open-label trials reported a
significant reduction in disability (with one also reporting
improvement on an index of disease progression).
Regarding other neurological diseases, one cohort study assessed
the association between consumption of omega-3 fatty acids (from
fish, ALA, EPA, or DHA) and risk for Parkinson's disease but
found no significant associations. One case-control study found
a significant association between maternal fish consumption at
least once weekly throughout pregnancy and a lower risk of
cerebral palsy in the offspring.
The quantity and strength of evidence for the effects of omega-3
fatty acids on cognitive function and decline, dementia, and
neurological diseases vary greatly. Given the overall small
number of studies and generally poor quality of clinical trials,
substantive conclusions about the value of these compounds for
these conditions cannot be drawn.
Omega-3 fatty acids for organ transplantation [7]
Several laboratory, animal, and human studies suggest that
omega-3 fatty acids from fish oil may improve outcomes in organ
transplantation (e.g., decrease rejection; reduce
hyperlipidemia, hypertension, and blood viscosity; and decrease
the toxicity of the immunosuppressive agent cyclosporin A). The
Tufts EPC systematically identified studies of human subjects
who underwent transplantation and received a quantifiable amount
of omega-3 fatty acids. A total of 31 studies were included in
the review pertaining to transplantation of the kidney (23),
heart (6), liver (1), and bone marrow (1). All but one study
used fish-oil supplements at doses ranging from 1.2 to 5.4 g/day
EPA plus DHA, though in most the daily dose was 2-3 g.
No conclusive evidence was found suggesting specific benefits of
omega-3 fatty acid supplementation on any outcome evaluated in
any form of transplantation. The one possible exception was a
reduction in triglyceride levels in patients who underwent
kidney transplantation, which is consistent with the effects of
omega-3 fatty acids for other conditions. The supplements did
not cause clinically important interactions with cyclosporin A.
The quantity and quality of the evidence and its applicability
to current transplantation procedures were limited. All studies
were small and had methodological problems, such as the rigor
with which endpoints were defined and measured, and most studies
were not recent. Because the technology for transplantation
continues to improve, whether fish-oil supplementation is
beneficial with current procedures is uncertain. Furthermore, in
all studies the supplements were begun after transplantation.
Because it may take up to three weeks for omega-3 fatty acids to
affect cytokine production, supplementation before the
transplants might have influenced the outcomes.
Safety aspects of omega-3 fatty acids [3]
The Tufts EPC reviewed 148 studies to evaluate adverse
events-not including fishy aftertaste-from the use of omega-3
fatty acid supplements (typically fish oils). More than half
(77) reported that no adverse events had occurred. In total,
about 10,000 subjects had taken these supplements in various
forms and dosages ranging from 0.3 to 8 g/day for at least one
week to more than seven years. Most studies were small, with a
few dozen subjects receiving supplements for less than six
months.
In general, side effects were minor, primarily gastrointestinal
in nature (such as diarrhea), and reported by fewer than 7% of
subjects. The supplements were not associated with serious
adverse events such as death, life-threatening illness,
significant disability, or handicap. Omega-3 fatty acids did not
affect the frequency of bleeding events. However, several cases
of clinical bleeding in two RCTs were reported where patients
also took warfarin or aspirin daily; the bleeding (e.g., at the
site of a wound or into the gastrointestinal tract) was
typically mild.
The Tufts EPC concluded that adverse events related to
consumption of fish-oil or ALA supplements appear to be minor
and can be managed by reducing the dose or discontinuing the
supplement. It noted, however, that adverse event data are
incomplete because many studies did not adequately report this
information, especially for subjects who withdrew before study
completion.
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